.beta.-catenin is a cytoplasmic protein that is critical for classical cadherin-mediated intercellular adhesion. Inside the cell, a .beta.-catenin/.alpha.-catenin complex interacts with the second cytoplasmic domain (CP2) of the classical cadherins. In the absence of this .beta.-catenin/.alpha.-catenin complex, the classical cadherins cannot promote cell adhesion (see Wheelock et al., Current Topics in Membranes 43:169-185, 1996).
In addition to its role in cell adhesion, .beta.-catenin is also a key component of certain cellular signaling pathways, leading to activation of gene expression and a variety of developmental and disease processes, such as differentiation, cancer and Alzheimer's disease. In particular, .beta.-catenin functions in Wnt-mediated signaling, associating with LEF-1/TCF DNA binding proteins to form a transcription factor (see Willert and Nusse, Genetics and Development 8:95-102, 1998). .beta.-catenin-mediated signaling is involved in a variety of developmental processes, including cellular differentiation. For example, skin cells expressing a stabilized form of .beta.-catenin display increased hair growth (Gat et al., Cell 95:605-614, 1998; Ono et al., Cell 95:575-578, 1998). Thus, therapies based on modulating .beta.-catenin mediated gene expression have potential for altering cell differentiation and, in certain instances, hair growth. Such therapies could further be used in the treatment of cancer and Alzheimer's disease. However, there are presently no available therapies for inhibiting .beta.-catenin-mediated signaling.
Accordingly, there is a need in the art for improved methods for modulating .beta.-catenin-mediated signal transduction and cellular differentiation. The present invention fulfills this need and further provides other related advantages.